CN109477051A - Fluid filter system with integrated discharge function - Google Patents
Fluid filter system with integrated discharge function Download PDFInfo
- Publication number
- CN109477051A CN109477051A CN201780040581.3A CN201780040581A CN109477051A CN 109477051 A CN109477051 A CN 109477051A CN 201780040581 A CN201780040581 A CN 201780040581A CN 109477051 A CN109477051 A CN 109477051A
- Authority
- CN
- China
- Prior art keywords
- liquid
- bioreactor
- fluid
- filter
- charge pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000012530 fluid Substances 0.000 title claims abstract description 45
- 239000007788 liquid Substances 0.000 claims abstract description 200
- 230000033001 locomotion Effects 0.000 claims abstract description 38
- 238000004891 communication Methods 0.000 claims abstract description 6
- 238000004113 cell culture Methods 0.000 claims description 28
- 239000012930 cell culture fluid Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 239000000758 substrate Substances 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 3
- 230000003833 cell viability Effects 0.000 claims description 2
- 235000015097 nutrients Nutrition 0.000 claims description 2
- 230000009897 systematic effect Effects 0.000 claims 1
- 238000001914 filtration Methods 0.000 abstract description 16
- 210000004027 cell Anatomy 0.000 description 34
- 230000006870 function Effects 0.000 description 19
- 238000009295 crossflow filtration Methods 0.000 description 18
- 230000010412 perfusion Effects 0.000 description 12
- 239000001963 growth medium Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/10—Perfusion
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/10—Separation or concentration of fermentation products
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D35/00—Filtering devices having features not specifically covered by groups B01D24/00 - B01D33/00, or for applications not specifically covered by groups B01D24/00 - B01D33/00; Auxiliary devices for filtration; Filter housing constructions
- B01D35/26—Filters with built-in pumps filters provided with a pump mounted in or on the casing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D37/00—Processes of filtration
- B01D37/04—Controlling the filtration
- B01D37/045—Controlling the filtration by level measuring
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D37/00—Processes of filtration
- B01D37/04—Controlling the filtration
- B01D37/046—Controlling the filtration by pressure measuring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/44—Means for regulation, monitoring, measurement or control, e.g. flow regulation of volume or liquid level
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Sustainable Development (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Fluid filter system of the invention includes: bioreactor；Filter is configured to filter the liquid passed through from it；Charge pump is configured between the bioreactor and the filter mobile liquid；Liquid line provides the fluid communication between the bioreactor, the charge pump and the filter；And exhaust outlet, it is arranged on the liquid line, the exhaust outlet is configured to provide the mode for selectively removing liquid from system under the movement of the charge pump.Using fluid filter system of the invention, filtering and discharge function can carry out under the movement individually pumped, thereby dramatically reduce the complexity and cost of required component.
Description
Invention field
The present invention relates to the fluid filter system for filtering liquid, the liquid is for example accommodated in bioreactor
Cell culture.
Background of invention
System for filtering liquid is well known in the art, wherein they using have separation, concentration or
Remove many different forms of the exemplary functions of the component of liquid, mixture or suspension.Such system is applied to biology
To extract certain biologics in technology and pharmaceuticals industry, such as the albumen generated in bioreactor using cell culture
Matter.
In traditional batch feed bioreactor system, cell batch culture, thus cell inoculation to fresh cultured
In base, and cell quickly enters growth period, they consume culture medium nutriment and in addition to dividing during this growth period
Except the target protein secreted, Waste buildup is in culture.Over time, become, cell transits to stationary phase, then by
It exhausts in cell culture into the decline phase.In end of run, divide using protein as a batch from cell culture clock
From.The problem of such system, especially in the case where usually having the animal cell culture compared with poor efficiency, being can be with
The limited yield of the purpose biologic of realization.
It is known alternative system that bioreactor, which is perfused, and wherein cell keeps supplementing culture simultaneously in culture
Base provides the required biologic of higher yields so that maintaining high cell concentration in longer time section.In order to tie up
Keep steady fixed cell culture condition, needs to filter with the purification of certain ingredients for cell culture medium, selective removal and dense
Contracting allows to supplement cell culture with fresh culture and can remove used culture medium.
The representative filtration systems that use are using pump in perfusion bioreactor, by filter by cell culture from life
It removes in object reactor, is removed from system including the filtrate of waste or target product, and the delay including living cells
Object is back to bioreactor.Individual system supplementing culture medium nutrients be may then pass through to maintain cell culture
Stable equilibrium state.Such prior-art devices generally use tangential flow filtration, and wherein most feeding flow tangentially passes through
The surface of filter.Such a system provides a kind of mild filter method, this method will not make fragile zooblast by
The very big power of cell may be damaged.In addition, liquid pass through filter tangential flow ensure in filter may cause it is stifled
The deposit of plug is flushed away during the filtration process, increases the time span of filtration system sustainable operation.Such system can be with
It is arranged so that the flowing of liquid on a direction around circuit, cycles through filter from bioreactor and is back to
(it is referred to as generic term " tangential flow filtration " or TFF) to bioreactor.Or such arrangement can be used, wherein only making
With the singular association between bioreactor and filter and flow direction replaces, so that liquid is marched to from bioreactor
Filter and along identical route back to bioreactor (referred to as " alternately tangential flow filtration " or ATF).
In such perfusion system, once required cell density is realized in bioreactor vessel, it may be desirable to
Prevent its rising higher.In order to provide this function, the system of the prior art is generallyd use by periodically or with restriction
Cell culture is given off system to reduce the mode of cell density by flow velocity.Flow velocity can be selected based on growth rate to incite somebody to action
Cell density is limited to desired value.Realize discharge usually using dip-tube, by the dip-tube, individual pump (such as only
Peristaltic pump for this purpose) movement under cell culture is removed from bioreactor.
This known emptying pump arrangement has several drawbacks in that.Increasing by the second pump especially to provide discharge function and increase is
The cost and complexity of system.Other than common filter process, it, which is also added, required manually controls degree or control row
The level and complexity of automation needed for playing function.In addition, this arrangement needs the additional port in bioreactor,
It increases the pollution risk of cell culture and increases the quantity for the component that must be sterilized between use.
Therefore, for provide selectively emigrated cells culture mode with keep the cheap of required cell density and
There are demands for perfusion filter system easy to implement.Being further desirable to the system reduces pollution present in prior art systems
Possibility, and reduce the complexity and/or required manual intervention degree of automation.It would also be desirable to provide a kind of simple discharge system
System, which can integrate in automated system, and can use under two kinds of operation modes of ATF and TFF, and hardly
It needs or does not need to be adjusted system.
Summary of the invention
The present invention is intended to provide a kind of filtration system, has simple design, reduce suitable and disposable
The quantity and complexity for the component that system is used together.The automation of component also should be simple, to reduce required manual intervention
Degree, and eliminate the demand to complex control system.Another important goal be reduce bioreactor on port number with
A possibility that reducing pollution.
According to the first aspect of the invention, the fluid filter system 100 for cell culture fluid to be perfused is provided, is wrapped
Include: bioreactor 130 is used to accommodate cell culture fluid；Filter 140, be disposed for filtering pass through from it is thin
Born of the same parents' culture solution；Charge pump 110 is configured between the bioreactor 130 and the filter 140 mobile cell culture
Liquid；Liquid line 150 provides the fluid communication between the bioreactor 130, charge pump 110 and filter 140；With
And exhaust outlet 180, it is arranged on the liquid line 150, the exhaust outlet 180 is configured to provide in the charge pump
From the mode of the system 100 selectively emigrated cells culture solution under 110 movement.
Using fluid filter system according to the present invention, filtering and discharge function can under the movement individually pumped into
Row, thus the complexity and cost of component needed for significantly reducing.Which also reduces the components that may need to sterilize between use
Quantity, reduce downtime, make it possible higher output.Further, since exhaust outlet setting is in pump and life
On liquid line between object reactor, therefore the additional port on bioreactor is not needed, therefore significantly reduce
A possibility that pollution for the cell culture being accommodated therein.It can be by under the regular event of pump according to the system of this system
Exhaust outlet is opened to automate in a simple manner to remove liquid.
Certain embodiments of the present invention provides the fluid filter system for cell culture to be perfused comprising: injection
Pump comprising gas chamber and removable plunger, wherein the gas chamber has in the hole of first end, and the plunger exists
Sealing is formed in the inner wall of the chamber；Liquid chamber, there are two opening, the openings to be located at the opposite of the chamber for tool
End, and the first opening is connected to the hole of the gas chamber；Bioreactor is opened with the second of the liquid chamber
Mouth is in fluid communication；Filter is arranged to filter the liquid passed through between the bioreactor and the liquid chamber, institute
Stating filter includes the permeant outlet for removing filtered liquid；Wherein the plunger is to cause mutually meeting the tendency of for gas
Dynamic reciprocating motion and it is moveable, the corresponding sports of the gas are handed between the liquid chamber and the bioreactor
Liquid is alternately driven, so that liquid passes through the filter, and filtered liquid can be removed via the permeant outlet
Body, the system further comprise exhaust outlet 180, and the exhaust outlet 180 is configured to provide and select under the movement of charge pump
Selecting property from the mode of the 100 emigrated cells culture of system.
Brief description
Embodiments of the present invention only will be described with reference to the drawings by embodiment now, in which:
Figure 1A schematically shows the first embodiment of fluid filter system of the invention；It can be with alternately tangential mistake
The operation of filter mode；
Figure 1B schematically shows the embodiment of fluid filter system of the invention, can be with wherein liquid in circuit
The tangential flow filtration mode of middle circulation operates；
Fig. 2 schematically shows the embodiments of liquid of the invention filtering, are incorporated to two valves to provide exhaust outlet；
Fig. 3 schematically shows another embodiment of fluid filter system of the invention, in filter and biology
Syringe pump and exhaust outlet are incorporated between reactor.
Fig. 4 schematically shows another embodiments of fluid filter system of the invention, in liquid return line
On be incorporated to folder valve and exhaust outlet；And
Fig. 5 schematically shows another embodiment of fluid filter system of the invention, is configured to provide ATF simultaneously
Exhaust outlet is incorporated on the liquid return line from second liquid chamber.
The detailed description of embodiment of the present invention
It is described below in attached drawing, describes certain embodiments of the present invention.It will be appreciated, however, that the present invention is unlimited
In described embodiment, and some embodiments can not include all features described below.However, it will be apparent that
Be, without departing substantially from wider range of spirit and scope of the invention described in appended claims, can herein into
Row various modifications and change.
Figure 1A and Figure 1B is shown respectively with the sheet of alternately tangential flow filtration (ATF) mode and tangential flow filtration (TFF) mode
The operating principle of the fluid filter system 100 of invention.Fluid filter system 100 includes charge pump 110,130 and of bioreactor
Filter 140, wherein charge pump is configured to move liquid from bioreactor 140 by filter 140 via liquid line 150
Out, the liquid line 150 provide between bioreactor 130, filter 140 and charge pump 110 needed for fluidly connect.Institute
Stating filtration system further comprises the exhaust outlet 180 being arranged on liquid line 150.The exhaust outlet 180 is configured to permit
Perhaps liquid is selectively removed from system 100 so that under normal operation when liquid under the movement of charge pump along liquid line
When road is mobile, the exhaust outlet 180 can be opened, so that liquid is pumped out the system 100.
In the exemplary arrangement of Figure 1A and Figure 1B, exhaust outlet 180 is arranged to the outlet 180 on charge pump 110, but
It is at any point that it can be placed on liquid line 150.Permeant outlet 141 is also shown in embodiment shown in Fig. 1,
Filtered penetrant can be removed from filter 140 by the permeant outlet 141.External penetration pump 142 can be used
Filtered penetrants are extracted in passing through the outlet 141, and are existed as the well known elements separated with perfusion and discharge function
Except the present invention.
With use independent liquid line (such as dip-tube, the liquid under the movement of the second pump into bioreactor 130
Exhaust through system) prior art systems it is different, present invention only requires single pumps to provide filling of the liquid by filter
Note and discharge function.
Figure 1A, which is shown, to be arranged to provide the system of the invention of ATF, wherein the movement pumped is alternately, so that liquid flow
The direction for crossing filter periodically inverts.Therefore, liquid is along the single liquid between bioreactor 130 and filter 140
Body route 150, which moves back and forth, to be passed through filter 140 to pump 110 and returns.In this embodiment, exhaust outlet is set as charge pump
Additional outlet on 180, liquid can by the egress selection be transferred out from system 100, rather than pass through liquid
Body route 150 returns.This can for example be achieved in that when such pump direction makes influence liquid be back to biology instead
Answer device 130 it is mobile when, open pump 110 on port liquid is guided out system.
Figure 1B is shown in which that component is arranged to and provides the system of the invention of TFF, and wherein circuit is provided with liquid line
Road 150, liquid can recycle between bioreactor 130, filter 140 and pump 110 around the circuit, so that liquid is with single
Direction is mobile to pass through filter 140.Equally, in this embodiment, exhaust outlet 180 is set as additionally going out on charge pump 110
Mouthful.As described above, charge pump 110 is used to drive the liquid around liquid line anti-from biology during the normal use of system
It answers device 130 to pass through filter 140 and is back to bioreactor 130.When needing to discharge, such as in order to stablize cell culture
In cell density, the exhaust outlet 180 on pump can be opened, so that liquid is directed out system rather than continues around liquid
Route 150 recycles.
Fig. 2 schematically shows a kind of plain modes that wherein discharge function can be controlled；It is shown in this figure
The case where example T FF system of Figure 1B.In this embodiment, the first folder valve 181 is arranged on exhaust outlet 180, and the
Two folder valves are arranged in a part of the liquid line 150 after following charge pump 110 in liquid flow direction closely.In system 100
Normal operating during, the first folder valve 181 is closed, and the second folder valve 182 is opened, so that charge pump is for being driven around liquid
The liquid in 150 circuit of route, so that liquid passes through filter 140 and can remove penetrant.When needs are removed from system
When liquid, such as in order to reduce cell density, valve 182 can be pressed from both sides by second on closing liquid route and opens exhaust outlet
On the first folder valve 181 carry out emissions operation so that by exhaust outlet 180 by liquid under the regular event of charge pump 110
Body is transferred out of system.Liquid flows in and out bioreactor 130 by the way that recirculation circuit is perfused, therefore can independently control
Pass through the flow of exhaust outlet 180.
Fig. 3, which is shown, is configured to provide another embodiment of the filtration system of the invention of ATF filter process.In the cloth
In setting, liquid is driven by the syringe pump 110 including plunger 112 and gas chamber 111, wherein the inner wall shape of plunger and chamber 111
Pass through chamber 111 at sealing and being configured to movement air is discharged by the hole 113 for being located at one end.Plunger 12 can be installed
On piston rod 114, needed for the piston rod 114 drives along the long axis setting of chamber 111 and by motor 115 to provide
Alternating movement.Hole at one end of gas chamber 111 and liquid chamber 120 are in fluid communication, the liquid chamber 120 again with mistake
Filter 140 and bioreactor 130 connect.Therefore, appearance is passed to by the alternating movement of the gas of the movement driving of plunger 112
The liquid being contained in liquid chamber 120, to be handed between bioreactor 130 and liquid chamber 120 along liquid line 150
The liquid is alternately driven, so that it passes through filter 140.Therefore, the direction of liquid replaces with the movement of plunger 112 in system.
The movement in plunger 112 towards hole 113 causes gas to enter liquid chamber, drives fluids through filter to bioreactor, and
And plunger 112 causes gas to exit liquid chamber 120 far from the movement in the hole, so that liquid is mobile from bioreactor 130
By filter 140 to fill liquid chamber 120.
Different from the embodiment of front, exhaust outlet 180 is not arranged on pump 110 in the system of figure 3, but is arranged
On liquid line 150 between filter 140 and bioreactor 130.Exhaust outlet 180 can be simply by filter
Band valve interconnecting piece in liquid line 150 between 140 and bioreactor 130 provides.Liquid line, which is divided into, is back to biology
The first line 152 of reactor 130 and the second drain line 183 for being guided out system.It can be again by the row of being separately positioned on
The first folder valve 181 and the second folder valve 182 on the returning part of unwrapping wire road 183 and liquid line 152 discharge to simply implement
Function.The opening and closing of folder valve 181,182 can mutually be cooperateed with the movement of charge pump.The system for filtering liquid just
It is often used down, closes the first folder valve 181 and opens the second folder valve 182, so that liquid is along fluid chamber under the movement of pump 110
Liquid line 150 between room 120 and bioreactor 130 is mobile by filter 140.When needs remove liquid from system
When, the first folder valve 181 on drain line 183 is opened, and the second folder valve on the returning part 152 of closing liquid route 150
182.When plunger 112 is mobile towards hole 113, liquid is along liquid line 150 and pumping-out line 183 from 120 quilt of liquid chamber
It drives and leaves system.Valve can be cooperateed with the movement of pump, so that only when the plunger of pump 112 is mobile towards hole 113, the row of opening
Unwrapping wire road 183 (and closing return line 152).As all embodiments of the invention, exhaust outlet 180 and pump 110
Collaborative Control can be provided manually by user or be automatically provided by the configuration of external control system.
It is different to provide the prior art systems of discharge function from wherein needing individually to pump, again in this arrangement
In, it does not need to provide the additional pump or external cellular moving-out device for being exclusively used in discharging the system.
Fig. 4 shows the another exemplary filtration system of the offer TFF of deployment cost invention.The system of Fig. 4 is similar to Fig. 3
Arrangement be incorporated with syringe pump 110, but the difference is that the second hole 213 is located at the phase in gas chamber 111 with the first hole 113
At opposite end.Piston rod 114 is " through rod " axially across chamber 111, and wherein plunger 112 is placed on the middle section of bar 114,
So that it is alternately mobile by chamber 111 between opposite first end and second end.Due to the first hole 113 and the second hole
213 are located near the opposite both ends of chamber 111, therefore gas is discharged by a hole, while being inhaled into another hole.The
One hole 113 and the second hole 213 can be respectively connected to the first liquid chamber 120 and second liquid chamber 220, respectively to be similar to
Mode described in reference diagram 3 connects.Therefore the movement of plunger 112 leads to the liquid being contained in liquid chamber 120,220
By 122,222 discharge of opening, while liquid is inhaled into chamber 220,120 by the opening of another liquid chamber.
Fig. 4 also show liquid chamber 120,220 how can be connected to filter 140 and bioreactor 130 with
Continuous pouring is provided in TFF arrangement.There are interconnecting pieces in the liquid line for the opening 122,222 for leaving each chamber, so that
Each chamber is divided into two lines road, is connected to the inlet line 153,253 of main fluid intake route 151 and is connected to main liquid and returns
The egress line 154,254 on loop line road 152.Inlet line 153,253 and egress line are opened and closed by using valve system 160
Road 154,254 controls the flowing of the liquid between liquid chamber and the rest part of system.In this embodiment, valve system by
Multiple flow control valves 162,163 (such as other folder valves) provide, with the flowing of the liquid in control system.With plunger 112
It is moved to the right side of chamber 111, first flow control valve 162 is open, and second flow control valve 163 is to close.
Then liquid is drawn through intake route 151 via filter 140 from bioreactor and passes through entrance 153 into the first liquid
Chamber.
Liquid is discharged by being connected to the outlet 254 of the second liquid chamber of liquid return line 152 simultaneously, returns liquid
It is back to bioreactor 130.It is then shut off first flow control valve 162 and opens second flow control valve 163, while plunger
112 are moved to the left towards the first end of chamber 111.Therefore, liquid is extracted out from bioreactor 130, simultaneously by filter 140
Enter second liquid chamber 220 via inlet line 253.Liquid passes through 154 row of egress line of the first liquid chamber 120 simultaneously
It is back to bioreactor out and via return line 152.By the operation and the syringe pump 110 that make flow control valve 162 and 163
Movement it is synchronous, effective no pulse continuous T FF may be implemented.
Similar to the arrangement of Fig. 3, for the ease of the discharge of system, band valve interconnecting piece is provided in return line 152, it will
Liquid chamber 120,220 is connect with bioreactor.As described above, the first branch in connection return line 152 is so as to just
Liquid is often back to bioreactor 130 under operation, fluid is guided out system by drain line 183 by another branch.
Branch in return line 152 may be provided with the first folder valve 181 and the second folder valve 182, the first folder valve 181 and the second folder valve
182 can open and close route to control discharge function.In the normal operation period, it closes the first drain line and presss from both sides valve 181, and
Open the second return line folder valve 182.When discharging cell, opens drain line folder valve 181 and close return line folder valve
182, so that liquid is released liquid chamber and passes through exhaust outlet 183 by the movement of syringe pump, rather than it is back to biological respinse
Device container 130.It is different from the embodiment of Fig. 3, in the arrangement of Fig. 4, regardless of syringe pump direction can be carried out cell row
It puts, because the two sides of gas chamber 111 are connected to liquid chamber 120,220, so that for two movement sides of plunger 112
To liquid is driven all along return line 152.
The arrangement of Fig. 4 additionally provides other functions.During perfusion, liquid constantly extracts (penetrant) out from system,
And it is supplemented by increasing culture medium conveying.Two kinds of pump rates are all controlled, but in prolonged experiment, if
The flow velocity Incomplete matching of penetrant and pump, then the culture volume in bioreactor 130 can change.Ensure to cultivate object
A kind of method for not declining of product be constantly by culture medium overfeeding into bioreactor 130, and periodically by cell from
It is discharged in bioreactor 130.This can use the movement reversal flow control of Fig. 4 being arranged through first relative to plunger 111
The sequence of valve 162,163 is realized.By configuring flow control valve 162,163 in this way, in the movement of charge pump 110
Under, liquid is extracted from bioreactor 130 by the first liquid chamber 120 and second liquid chamber by liquid return line 152
In room 220.After removing liquid in bioreactor 130, the first folder valve can opened by liquid return line 152
181 and the second folder valve 182 is closed, while restoring the normal sequence of flow control valve 162,163 and charge pump 110, so that liquid
System is moved out of by drain line 183 under the movement of charge pump 110.
There is the 152 (example of return line of the fixed height h of the interior substrate 131 more than bioreactor 130 by providing
Such as in the form of dip-tube), liquid can be extracted by return line 152, until it reaches being somebody's turn to do in bioreactor 130
Known level h.Or, thus it is possible to vary the length of return line in bioreactor allows to adjust the end of return line 152
The distance between the substrate of portion 153 and bioreactor 131 h.In this way, when as described above by return line 152 from
When bioreactor 130 removes liquid, the known altitude h that liquid level can be adjusted in bioreactor 130.
Fig. 5 shows another embodiment, using the revision of the arrangement of Fig. 4, is configured to provide for ATF rather than TFF.
With latter arrangement, syringe pump 110 has the first hole 113 and the second hole 213 in the opposite end of gas chamber 111, described
Hole is respectively connected to the first liquid chamber 120 and second liquid chamber 220.In this arrangement, the first liquid chamber 120 via
Filter 140 is connected to bioreactor 130 by liquid line 151, alternately drives liquid by the liquid line 151
To provide ATF.Second liquid chamber 220 is connected to bioreactor 130 via exhaust outlet 180.It, can be with using this arrangement
Implement two different discharge process.
It is possible, firstly, to integrated cell discharge is provided during filtering, wherein when liquid is discharged from liquid chamber 120,
First flow control valve 164 is closed, and opens second flow control valve, open simultaneously discharge folder valve 181 and closes the line of return
Road presss from both sides valve 182, so that liquid is directed out exhaust outlet 183.Alternatively, may be implemented it is independent be emitted into liquid level, passing through row
Liquid is simply pumped into second liquid chamber from bioreactor 130 using second liquid chamber 220 before the discharge of discharge port 180
In room, and repeat until reaching required liquid level.
In more detail, by closing second flow control valve 165, first flow control valve 164 and mobile plunger are opened
112, with before being returned liquid along liquid line 151 by filter and returning to bioreactor 130, by liquid from life
Object reactor 130 is alternately pumped into the first liquid chamber 120 by filter 140 and provides ATF.In order to provide integrated row
Playing function presss from both sides valve 164 and 182 by closing, opens valve 165 and 181, then pass through when liquid is discharged from the first liquid chamber
First liquid chamber 120 is emptied by check-valves 168, liquid is guided out exhaust outlet.Check-valves 168 makes to stay in pipe branch
Discharge cell " dead volume " minimize, and prevent discharge cell any " reflux ", the cell of the discharge time
Stream can pollute the cell culture that the remainder of the first liquid chamber 120 is flowed in and out from perfusion filter device 140.Check-valves
It is not used in the flow direction of control ATF perfusion functional.
It is emitted into liquid level in order to provide, (when the arrangement is configured for TFF, has and uses using dip-tube 152
Make the additional functionality of return line 152).Second liquid chamber 220 is via open return line valve 182 (and 165 He of valve
181 close) cell culture is extracted from the dip-tube 152 of shortening.Then pass through closing valve 182 and open drain valve 181 to arrange
Empty second liquid chamber 220.The process is repeated, until other no liquid can be drawn in upper dip-tube, because liquid level is
Drop to the end of pipe or less.Therefore, the amount of liquid in bioreactor can be adjusted and return in bioreactor 130
The liquid level of height h.
The embodiment of the present invention may further include one or more sensors 190, one or more of sensors
190 are configured as one or more parameters of sensing system.Although the sensor 190 in Fig. 3 and Fig. 4 is arranged to sensing one
Or the external sensor of the liquid level in multiple liquid chambers 120,220, but can additionally be incorporated to and be configured to sensing such as cell
The sensor of the other parameters of density, cell viability and pressure.As described above, the movement of plunger, motor and flow control
Control with the sequence of folder valve can be carried out manually by user or be carried out automatically by control unit.Control unit can permit planning
ATF, TFF, cell discharge and the required stage of Liquid level.The control of above-mentioned various operations can also automate, in response to passing
Sensor sensing data and control various functions.For example, when sensing is statistics indicate that cell density rises to over predetermined threshold
When, control system can start cell discharge to reduce cell density, until reaching as what sensor was measured scheduled connects
By level.Can control exhaust outlet so that liquid outflow system can be it is continuous or periodic.
In all above-described embodiments of the invention, the pipeline for being formed together liquid line with folder valve be can be set can be more
In the box changed.For example, labware needs six roots of sensation pipeline correct by four folder valves in the embodiment of Fig. 4 and Fig. 5
Wiring.In order to eliminate a possibility that operator mistakes, and the task of operator is made to become very easy, pipeline is preloaded into one
In secondary property box, the box is the component part of the labware.Operator need to only load box and (spend several seconds
Simple task), steadily and correctly to carry out all necessary connections.
In all above-described embodiments of the invention, entire product contact path (that is, directly contacted with cell culture
Component) it can be the disposable of the single use including the labware.The labware is designed to make
Technical ability needed for bioreactor 130 and perfusion filter device 140 are connected to machine and time minimize, the machine transfer tube
(while keeping sterile) carries out all environment, deflation, charging, stirring, circulation and sensing function needed for the process to realize.Pump
110 can be the fixed part of the machine in itself, do not need to clean or sterilize, and can be via the collection in labware
At sterilizing filter be connected to the labware.Cell culture is not passed through mechanical pump (for example, diaphragm, impeller or compacted
Dynamic, cell can be destroyed)-by the way that cell culture is sucked out from bioreactor 130, by perfusion filter device 140,
Then it " blows " and is back in reactor 130, or by filter 140 (" ATF ") or via individual return line 152
(" TFF ") returns to realize flowing.Mere contact with cell culture is sterile tube and other disposable modelings being intended for single use
Expect component and clean filtered air.
For ATF or TFF, normal perfusion function needs only one liquid chamber.However, by using second chamber, it is right
Cell culture is passed through into perfusion filter from the suction of bioreactor 130 simultaneously in " quasi-continuous " flowing-that TFF may be implemented
Device 140 enters in a liquid chamber 120, and the cell culture from previous circulation can be returned from second liquid chamber 202
To bioreactor 130.
In general, perfusion experiment sustainable 30 to 60 days, cell culture is continuously flowed into and trickle chamber.Even if chamber
The material (such as polypropylene) of room has low-surface-energy, and cell culture is not easy to be bound to surface, but prolonged
In experiment, cell culture can start to accumulate on chamber wall.Volume in chamber can be decreased to unacceptable low by this
Level, and/or may potentially have an adverse effect to the cell for flowing into chamber.Fluorination work can be used on liquid chamber
Surface polymer is effectively changed into PTFE by skill, to reduce the cell combination on fluid chamber locular wall.
Using fluid filter system of the invention, simple low cost arrangement is provided for promoting cell to discharge.With need
Want the prior art systems of additional pump for the emigrated cells culture from bioreactor different, as use of the present invention
Arrangement: it wherein can use charge pump the movement extracting liq from system.It reduce it is relevant to additional pump is incorporated at
This and complexity, and further reduced the chance of failure and between operation to equipment sterilize required shutdown when
Between.Different from prior art systems, system of the invention does not need the additional port of bioreactor, therefore the possibility polluted
Property further decreases.In addition, user's degree of participation or the degree of automation needed for reducing control filtering and discharge function, because
These can be provided by controlling single pump and relevant valve.Arrangement of the invention, which additionally provides, to be adjusted in bioreactor
Liquid level mode, increase with reduce quantity component additional function.
Claims (14)
1. the fluid filter system (100) for cell culture to be perfused, comprising:
Bioreactor (130), is used to accommodate cell culture fluid；
Filter (140) is configured to filter the cell culture fluid passed through from it；
Charge pump (110) is configured between the bioreactor (130) and the filter (140) mobile cell training
Nutrient solution；
Liquid line (150) provides the bioreactor (130), the charge pump (110) and the filter (140)
Between fluid communication；And
Exhaust outlet (180) is arranged on the liquid line (150), and the exhaust outlet (180) is configured to provide in institute
It states under the movement of charge pump (110) from the mode of the system (100) selectively emigrated cells culture solution.
2. fluid filter system as described in claim 1, wherein the exhaust outlet is by additional in the charge pump (110)
Outlet provide.
3. fluid filter system as claimed in claim 1 or 2, wherein the exhaust outlet (180) further comprises
First folder valve (181), is configured to selectively open and close the exhaust outlet.
4. fluid filter system as claimed in claim 3 further comprises relevant second folder valve (182), second folder
Valve is configured to close the liquid line (150) when first folder valve (181) is opened.
5. fluid filter system as described in any one of the preceding claims, further comprises
One or more sensors (190), one or more of sensors (190) are configured to measure the liquid in the system
One or more parameters.
6. fluid filter system as claimed in claim 5, wherein the parameter sensed by one or more of sensors (190)
Including one of the following or multiple:
Liquid level, pressure, cell density, cell viability.
7. fluid filter system as described in any one of the preceding claims, wherein the liquid line (150) includes
Fluid intake route (151) extracts cell from the bioreactor (130) by the fluid intake route (151)
Culture solution；And
Cell culture fluid is back to the biological respinse by the liquid return line (152) by liquid return line (152)
Device (130)；Wherein
The fluid intake route (151) and liquid return line (152) provide together the connection bioreactor (130),
The circuit of the filter (140) and the charge pump (110), during use, under the movement of the charge pump (110),
Cell culture fluid is flowed around the circuit.
8. fluid filter system as claimed in claim 7, wherein the exhaust outlet is arranged in the liquid return line
(152) on.
9. fluid filter system as claimed in claim 7 or 8, wherein the liquid line of return in the bioreactor
The end (153) on road (152) and the substrate (131) of the bioreactor separate specific height (h).
10. fluid filter system as claimed in claim 9, wherein the charge pump (110) is configured to by from the biology
The liquid via the liquid return line (152) emigrated cells culture solution and is guided out the discharge by reactor (130)
(180) are exported selectively to invert the circulation of the cell culture fluid in the system, thus by the bioreactor (130)
In liquid level be adjusted to specific height (h).
11. the method for emigrated cells culture solution from fluid filter system, the system comprises:
Bioreactor (130), is used to accommodate cell culture fluid；
Filter (140) is configured to filter the cell culture fluid passed through from it；
Charge pump (110) is configured between the bioreactor and the filter mobile cell culture fluid；
Liquid line (150) provides the bioreactor (130), the charge pump (110) and the filter (140)
Between fluid communication；And
Exhaust outlet (180) is arranged on the liquid line (150), and the exhaust outlet (180) is configured to provide from institute
With the stating Systematic selection mode of emigrated cells culture solution；The described method includes:
The charge pump (110) are operated, so that cell culture fluid passes through the filter via the liquid line (150) are mobile
(140)；
The exhaust outlet (180) are opened, so that the cell culture fluid is under the movement of the charge pump (110) from the liquid
Body route removes；
The exhaust outlet (180) are closed after the cell culture fluid for removing requirement in the system.
12. method as claimed in claim 11, wherein the system further comprises:
First folder valve (181), is configured to open and close the exhaust outlet (180)；
Second folder valve (182), is configured to open and close the liquid line (150)；The method further includes:
It opens first folder valve (181) and closes second folder valve (182), so that cell culture fluid is directed out the row
Discharge port (180).
13. the method as described in claim 11 or 12, wherein the system further comprises:
Fluid intake route (151), by the fluid intake route (151) from institute under the movement of the charge pump (110)
It states bioreactor (130) and extracts cell culture fluid；And
Liquid return line (152), will be thin under the movement of the charge pump (110) by the liquid return line (152)
Born of the same parents' culture solution is back to the bioreactor (130), the liquid return line in the bioreactor (130)
(152) substrate (131) of end (153) and the bioreactor (130) separates specific height (h)；Wherein
The fluid intake route (151) and liquid return line (152) provide together the connection bioreactor (130),
The circuit of the filter (140) and the charge pump (110), during use, under the movement of the charge pump (110),
Liquid is flowed around the circuit；And
The exhaust outlet (180) is arranged on the liquid return line；
The method further includes:
When second folder valve (182) is opened, the movement of the charge pump (110) is inverted, so that cell culture fluid passes through institute
It states liquid return line (152) to be extracted from the bioreactor (130), until liquid level is reduced to the specific height
(h)；
It closes second folder valve (182) and opens the first folder valve；And
The movement of the charge pump (110) is reset, so that liquid is transferred out of the row under the movement of the charge pump (110)
Discharge port (180).
14. the method as described in any one of claim 11 to 13, the fluid filter system further comprises:
One or more sensors (190), one or more of sensors (190) are configured to sensing and the liquid in the system
The relevant one or more parameters of body；The method further includes:
The exhaust outlet (180) is opened and closed according to the parameter sensed by one or more of sensors (190).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16180185 | 2016-07-19 | ||
| EP16180185.7 | 2016-07-19 | ||
| PCT/EP2017/068165 WO2018015405A1 (en) | 2016-07-19 | 2017-07-18 | Liquid filtration system with integrated bleed function |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109477051A true CN109477051A (en) | 2019-03-15 |
| CN109477051B CN109477051B (en) | 2022-05-03 |
Family
ID=56464124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780040581.3A Active CN109477051B (en) | 2016-07-19 | 2017-07-18 | Liquid filtration system with integrated drain function |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US11597904B2 (en) |
| EP (1) | EP3487979A1 (en) |
| CN (1) | CN109477051B (en) |
| WO (1) | WO2018015405A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952786A (en) * | 2021-10-21 | 2022-01-21 | 上海艾众生物科技有限公司 | Biological filtration system and control method thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3908389A4 (en) * | 2019-01-10 | 2022-11-16 | Repligen Corporation | Hollow fiber filtration systems and methods |
| US20220193582A1 (en) * | 2019-05-21 | 2022-06-23 | Repligen Corporation | Alternating tangential flow pumping method |
| US20210062133A1 (en) * | 2019-08-28 | 2021-03-04 | Nirrin Technologies, Inc. | Device and bioreactor monitoring system and method |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3472765A (en) * | 1968-06-10 | 1969-10-14 | Dorr Oliver Inc | Membrane separation in biological-reactor systems |
| WO1985001064A1 (en) * | 1983-08-25 | 1985-03-14 | Munir Cheryan | Continuous fermentation process |
| WO2009006909A1 (en) * | 2007-07-10 | 2009-01-15 | Nordbiochem OÜ | Process for producing organic acids by continuous fermentation |
| CN101985597A (en) * | 2010-09-08 | 2011-03-16 | 上海国强生化工程装备有限公司 | Animal cell reactor with bubble-free aerating system |
| CN102071137A (en) * | 2009-11-19 | 2011-05-25 | 上海坤巨科技发展有限公司 | Device and method for preparing stem cells through continuous perfusion bioreactor/tank (bag) system |
| CN103243027A (en) * | 2013-05-24 | 2013-08-14 | 中山大学 | Perfusion type bioreactor of double-layer circulating system and application method of perfusion type bioreactor |
| CN105586249A (en) * | 2016-03-07 | 2016-05-18 | 浙江大学 | Circulating perfusion biological reactor device capable of achieving circulating perfusion of three-dimensional support |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9109193B2 (en) * | 2007-07-30 | 2015-08-18 | Ge Healthcare Bio-Sciences Corp. | Continuous perfusion bioreactor system |
| ES2657055T3 (en) | 2007-08-09 | 2018-03-01 | Wyeth Llc | Use of perfusion to improve the production of a batch-fed cell culture in bioreactors |
| US20120295289A1 (en) * | 2009-11-13 | 2012-11-22 | The Governing Council Of The University Of Toronto | Device and method for culturing cells |
| US20140093952A1 (en) * | 2012-10-02 | 2014-04-03 | David Serway | Bioreactor Tangential Flow Perfusion Filter System |
-
2017
- 2017-07-18 EP EP17742419.9A patent/EP3487979A1/en active Pending
- 2017-07-18 WO PCT/EP2017/068165 patent/WO2018015405A1/en unknown
- 2017-07-18 CN CN201780040581.3A patent/CN109477051B/en active Active
- 2017-07-18 US US16/312,182 patent/US11597904B2/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3472765A (en) * | 1968-06-10 | 1969-10-14 | Dorr Oliver Inc | Membrane separation in biological-reactor systems |
| WO1985001064A1 (en) * | 1983-08-25 | 1985-03-14 | Munir Cheryan | Continuous fermentation process |
| WO2009006909A1 (en) * | 2007-07-10 | 2009-01-15 | Nordbiochem OÜ | Process for producing organic acids by continuous fermentation |
| CN102071137A (en) * | 2009-11-19 | 2011-05-25 | 上海坤巨科技发展有限公司 | Device and method for preparing stem cells through continuous perfusion bioreactor/tank (bag) system |
| CN101985597A (en) * | 2010-09-08 | 2011-03-16 | 上海国强生化工程装备有限公司 | Animal cell reactor with bubble-free aerating system |
| CN103243027A (en) * | 2013-05-24 | 2013-08-14 | 中山大学 | Perfusion type bioreactor of double-layer circulating system and application method of perfusion type bioreactor |
| CN105586249A (en) * | 2016-03-07 | 2016-05-18 | 浙江大学 | Circulating perfusion biological reactor device capable of achieving circulating perfusion of three-dimensional support |
Non-Patent Citations (1)
| Title |
|---|
| 肖成祖 等: "《细胞制药与尿激酶原》", 31 October 2011, 军事医学科学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952786A (en) * | 2021-10-21 | 2022-01-21 | 上海艾众生物科技有限公司 | Biological filtration system and control method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109477051B (en) | 2022-05-03 |
| EP3487979A1 (en) | 2019-05-29 |
| US20200181554A1 (en) | 2020-06-11 |
| US11597904B2 (en) | 2023-03-07 |
| WO2018015405A1 (en) | 2018-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109477051A (en) | Fluid filter system with integrated discharge function | |
| JP7298054B2 (en) | Disposable bioprocess systems that support bioactivity | |
| US4722902A (en) | Apparatus and method for culturing cells, removing waste and concentrating product | |
| US8501460B2 (en) | Bioreactor systems and disposable bioreactor | |
| US9663753B2 (en) | Tangential flow perfusion system | |
| CN103347595B (en) | Pneumatic alternating pressure theca cell piece-rate system | |
| JP2008539738A (en) | Supply system for cell culture modules | |
| US11560539B2 (en) | Reversible liquid filtration system | |
| CN109415673A (en) | Liquid filtering and pumping system | |
| CN108841727B (en) | CAR-T cell automatic preparation system based on micro-fluidic chip | |
| JP2021508594A (en) | Plunger pump pumping device for hollow fiber filters | |
| KR20200096656A (en) | Dual pumping arrangement for hollow fiber filters | |
| JP2007222063A (en) | Culture apparatus and method | |
| CN115786112A (en) | Differential pressure regulating system, continuous harvesting system and using method thereof | |
| CN214903162U (en) | Small-size aquatic organism breeding device | |
| JP7057423B2 (en) | Micro Alternate Tangent Perfusion Filters, Treatment Containers and Their Usage | |
| WO2018189398A1 (en) | Device for processing a liquid sample | |
| KR102351632B1 (en) | How to handle liquid samples | |
| CN218666101U (en) | Differential pressure regulating system and continuous harvesting system | |
| US11673083B2 (en) | Filtration system with selective flow reversal | |
| CN210008413U (en) | Automatic water changing device for fish exposure experiment | |
| JPH01206988A (en) | Culture apparatus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |